**4. Early embryonic period**

Zygote undergoes a set of mitotic division which is called "segmentation". With the first segmentation division, blastomere which is a two cell embryo forms. When the blastomeres proliferate in countless numbers it is called morula. Then, water diffusion starts in morula and a liquid filled blank which is called blastocele forms. When this blank forms, embryo is called as blastocyte [30, 32].

When blastocyte undergoes a mitotic division, liquid continues to accumulate in the blasto‐ cele and for this reason pressure inside the embryo increases. Proteolytic enzymes and blas‐ tocyte contraction and relaxation movements cause the tear of zona pelucida. When there is a little tear in zona pellucida, blastocyte goes out. This prolapsus which is called as hatching takes place between 9th and 11th days in cows. After this stage, embryo lives freely in ute‐ rus until implantation and feeds with uterus milk [14, 24, 30, 32].

15th to 17th days of the gestation is considered as the critical period. Embryonic deaths taking place in this stage causes dramatic economic losses. During this period, unless the signal to pre‐ vent the production of PGF2α is sent, endometrial luteolytic PGF2α release will be realized. For the continuation of gestation this endometrial PGF2α production must be hindered. Biology of this critical period is complex and affected from very different events. Forming of luteolysis or continuation of gestation is dependent on hormonal, cellular and molecular factors belonging to both mother and the embryo. In order to increase the pregnancy rate in artificial insemina‐ tion and embryo transfer, hCG, eCG and GnRH applications are done in this critical period. In these applications, while increasing progesterone amount, decreasing plasma estradiol 17 beta amounts and inhibiting PGF2α synthesis from endometrium is aimed [16].

Even in healthy cows in the first three weeks of pregnancy, more than 25% of the em‐ bryos cannot continue its development. While fertilization rate in cows with first service is 90%, calving rate is about 50-60% [4, 14]. In a study associated with this topic, it is report‐ ed that calving rate is 70% after insemination and most of the 30% of embryo losses take place in between 6th and 18th days [34]. If embryonic death happens before 16th - 17th days, cows continue to show estrus within normal intervals. However, if embryonic death hap‐ pens after 16th - 17th days, returning back to estrus cycle takes longer and cycle interval be‐

Nonsteroid Anti-Inflammatory Drugs to Improve Fertility in Cows

http://dx.doi.org/10.5772/51910

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There are plenty of factors that cause embryonic death in cows. These are; endocrine, genet‐ ic, intrinsic and extrinsic environmental factors, climate, stress, age, insemination time, se‐ men quality, infectious agents, nutrition, chromosomal anomalies. Especially, abnormal progesterone and estrogen profiles cause embryonic deaths. Moreover, in high producing cows steroid metabolism is faster because of liver blood circulation increase. And this causes

Low progesterone levels lead to death of embryo by causing excessive estradiol and PGF2α secretion. It is required that luteolytic effects of estradiol and PGF2α should be decreased in the early period after insemination in order for maternal recognition of pregnancy [36].

Researchers assert that low progesterone concentration before insemination period causes abnormal follicular development, elicit abnormal oocyte development in ovulatory follicle

Adequate secretion of progesterone in luteal period is vital for healthy ovulation, nutrition and survival of developing embryo. Low level of progesterone leads to embryonic death for

**1.** Low progesterone levels from ovulation to 6th day after the insemination causes the in‐

**2.** If progesterone is insufficient in pre-estrus period, uterus deprives of progesterone re‐ ceptors. As a result of this, in 4th – 9th days of post insemination excessive PGF2α secre‐

**3.** In 14th – 17th days which are the days of pregnancy recognition, cause of low pregnancy

**4.** Low progesterone levels in late embryonic period indicate imminent embryonic death

Oxytocin produced by corpus luteum stimulates the release of PGF2α from endometrium. PGF2α production depends on reaching of oxytocin receptor number to a threshold value. When these receptors in endometrium reaches a sufficient number, pulsatil secretion of

tion forms, and this makes both an embryotoxic and luteolytic affect.

rate is progesterone inadequacy and excessiveness of estradiol.

lower levels of progesterone in luteal period of estrus cycle [4, 35].

**7. Embryonic losses due to endocrinologic causes**

and ultimately, it causes early embryonic death [37-38].

hibition of embryo's development.

comes irregular [4].

reasons of:

[36, 39].
